老年人餐后不适综合征的治疗:一项多中心前瞻性随机对照临床研究

Treatment of postprandial discomfort syndrome in the elderly:a multi-centered prospective randomized controlled clinical study

目的评估米曲菌胰酶片治疗老年人餐后不适综合征(PDS)的有效性和安全性,及其与促胃肠动力药物的疗效差异。方法采用前瞻性随机对照试验设计。将老年PDS患者用随机数表法抽样分为3组,莫沙必利组采用枸橼酸莫沙必利片治疗(5 mg/次,3次/d,餐前服用,疗程2周),米曲菌胰酶片组采用米曲菌胰酶片治疗(244 mg/次,3次/d,餐中或餐后服用,疗程2周),联合治疗组采用枸橼酸莫沙必利片和米曲菌胰酶片治疗(用法用量同前,疗程2周)。采用改良的尼平消化不良指数(NDSI)评分标准,分别于治疗前和治疗1周、2周、停药4周后,对患者进行NDSI评分、不适强度评分和PDS评分,同时进行疗效分析和药物不良反应评估。结果全国16家三级甲等医院参加本研究,共有323例患者入组,其中,莫沙必利组105例,米曲菌胰酶片组109例,联合治疗组109例。研究对象中,男148例(45.8%),女175例(54.2%),年龄60~100(71.4±9.0)岁;3组的基线特征无差异。治疗后,3组的NDSI评分均明显下降(P<0.001);不论是米曲菌胰酶片组还是联合治疗组,治疗1周、2周的NDSI评分与莫沙必利组相比差异均无统计学意义(P>0.05)。3组的不适强度评分和PDS评分在治疗后均下降(P<0.001),其中联合治疗组的评分下降最明显;米曲菌胰酶片组第1周和第2周的不适强度评分和PDS评分均低于莫沙必利组[不适强度评分:第1周,4.0(2.8,8.0)分比6.0(3.0,10.0)分;第2周,3.0(0.0,5.0)分比4.0(2.0,6.0)分;P值均<0.05。PDS评分:第1周,6.0(3.0,9.0)分比7.0(3.5,10.5)分;第2周,3.0(0.0,5.0)分比4.0(2.0,7.0)分;P值均<0.05]。莫沙必利组、米曲菌胰酶片组和联合治疗组在治疗1周时的总有效率均超过15.0%,治疗2周时总有效率分别为55.2%、68.8%和73.4%,其中米曲菌胰酶片组和联合治疗组的2周总有效率均高于莫沙必利组(P=0.041和P=0.006)。停药后,莫沙必利组的复发率最高(9.5%),显著高于米曲菌胰酶片组(1.8%,P<0.05)和联合治疗组(1.8%,P<0.05)。3组均未见严重不良反应。结论米曲菌胰酶片可以安全、有效改善老年人PDS症状,其治疗老年人PDS的效果与莫沙必利相近,且不良反应少,复发率低。米曲菌胰酶片联合莫沙必利治疗老年人PDS的效果优于单用一种药物。

ObjectiveTo evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets(Combizym■)in the treatment of postprandial distress syndrome(PDS)in the elderly,compared with gastrointestinal motility drugs.MethodsA prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry(ChiCTR-IPR-16008185).The elderly patients with PDS were randomly divided into three groups,including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks;Combizym■ group with Combizym tablets 244 mg 3 times per day for 2 weeks;combined treatment group with both drugs and same doses for 2 weeks.The modified Nepean dyspepsia index(NDSI)score,discomfort intensity score and PDS score were calculated on patients before treatment,at the end of first and second week of treatment,as well as 4 weeks after treatment finished,respectively.Adverse effects were evaluated.ResultsA total of 323 patients from 16 tertiary hospitals in China were enrolled in this study.Among them,105 patients were in Mosapride group,109 in Combizym■ group and 109 in combined treatment group.There were 148 males(45.8%)and 175 females(54.2%)with median age 71.4±9.0 years(60-100 years).Baseline characteristics of three groups were comparable.After treatment,the NDSI scores in three groups all decreased significantly(P<0.001),while they were similar between groups(P>0.05).The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment(P<0.001),especially in the combined treatment group.Compared with Mosapride group,the scores in Combizym■ group decreased significantly after one or two weeks[discomfort intensity score:after one week,4.0(2.5,8.0)vs.6.0(3.0,10.0);after two weeks,3.0(0.0,5.0)vs.4.0(2.0,6.0);all P<0.05.PDS score:after one week,6.0(3.0,9.0)vs.7.0(3.5,10.5);after two weeks,3.0(0.0,5.0)vs.4.0(2.0,7.0);all P<0.05].The efficacy rate in all patients after first week of treatment was over 15.0%.The efficacy rates after two weeks were 55.2%,68.8%and 73.4%in Mosapride group,Combizym■ group and combined treatment group,respectively.After two week treatment,the efficacy rates in Combizym■ group(P=0.041)and combined group(P=0.006)were higher than that of Mosapride group.The recurrence rate of Mosapride group was 9.5%,which was significantly higher than that of Combizym■ group(1.8%,P<0.05)and combined treatment group(1.8%,P<0.05).There were no serious adverse effects in the three groups.ConclusionsThe efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients,with fewer adverse effects and low recurrence rate.Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.